Title

5-Hydroxytryptamine Interaction With The Nicotinic Acetylcholine Receptor

Department

neurobiology

Document Type

Article

Abstract

The present study examines the interaction of the neurotransmitter 5- hydroxytryptamine (5-HT) with muscle-type nicotinic acetylcholine receptors. 5-HT inhibits the initial rate of [125I]α-bungarotoxin binding to Torpedo acetylcholine receptor membranes (IC50=8.5±0.32 mM) and [3H]5-HT can be photoincorporated into acetylcholine receptor subunits, with labeling of the α-subunit inhibitable by both agonists and competitive antagonists. Within the agonist-binding domain, [3H]5-HT photoincorporates into αTyr190, αCys192 and αCys193. Functional studies using the human clonal cell line TE671/RD, show that 5-HT is a weak inhibitor (IC50=1.55±0.25 mM) of acetylcholine receptor activity. In this regard, agonist-response profiles in the absence and presence of 5-HT indicate a noncompetitive mode of inhibition. In addition, 5-HT displaces high affinity [3H]thienylcyclohexylpiperidine binding to the desensitized Torpedo acetylcholine receptor channel (IC50=1.61±0.07 mM). Collectively, these results indicate that 5-HT interacts weakly with the agonist recognition site and inhibits receptor function noncompetitively by binding to the acetylcholine receptor channel. (C) 2000 Elsevier Science B.V.

Publication Date

2-18-2000

Publication Title

European Journal of Pharmacology

ISSN

00142999

Volume

389

Issue

2019-02-03 00:00:00

First Page

155

Last Page

163

Digital Object Identifier (DOI)

10.1016/S0014-2999(99)00855-9

This document is currently not available here.

Share

COinS